rs9376165

Variant names:

• chr6-135921170-G-A
• rs9376165
• NM_018945.4:c.22-26294G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018945.4(PDE7B):​c.22-26294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,104 control chromosomes in the GnomAD database, including 1,724 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1724 hom., cov: 32)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 2 publications found

Genes affected

PDE7B (HGNC:8792): (phosphodiesterase 7B) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a cAMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family.[provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.22-26294G>A		intron_variant	Intron 1 of 12	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.22-26294G>A		intron_variant	Intron 1 of 12	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20927 AN: 151986 Hom.: 1721 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20954 AN: 152104 Hom.: 1724 Cov.: 32 AF XY: 0.140 AC XY: 10386 AN XY: 74334

African (AFR) AF: 0.133 AC: 5520 AN: 41520

American (AMR) AF: 0.202 AC: 3078 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.385 AC: 1982 AN: 5144

South Asian (SAS) AF: 0.244 AC: 1173 AN: 4804

European-Finnish (FIN) AF: 0.0553 AC: 586 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7922 AN: 67986

Other (OTH) AF: 0.132 AC: 280 AN: 2116

Alfa AF: 0.130 Hom.: 227

Bravo AF: 0.147

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.4
DANN	Benign	0.61
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9376165; hg19: chr6-136242308;